Zanubrutinib (BGB-3111) — a small molecule inhibitor of Bruton’s tyrosine kinase, or BTK, that is currently being evaluated in a broad late-stage clinical trials program globally, including in China, as a potential monotherapy and in combination with other therapies to treat various B cell malignancies.

The Role of BTK

BTK is a key component of the B-cell receptor, or BCR, signaling pathway and is an important regulator of cell proliferation and cell survival in various B cell malignancies. BTK inhibitors block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in certain malignant white blood cells called B-cells. Zanubrutinib is an orally active inhibitor that covalently binds to BTK, resulting in irreversible inactivation of the enzyme.

Zanubrutinib Clinical Trials

Zanubrutinib is in pivotal Phase 2 and Phase 3 trials in several B cell malignancies including: Waldenstrom’s macroglobulinemia (WM), treatment-naive mantle cell lymphoma (MCL), both front-line and relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), relapsed/refractory follicular lymphoma, marginal zone lymphoma, and diffuse large B-cell lymphoma.

For more clinical trial information please visit CLINICALTRIALS.GOV.

Zanubrutinib Monotherapy Trials

Zanubrutinib, as a monotherapy, is in pivotal Phase 3 trials globally in WM and front-line CLL/SLL, and in pivotal Phase 2 trials as a monotherapy in China in WM, relapsed or refractory CLL/SLL, and relapsed or refractory MCL.

Zanubrutinib Combinations

In Combination with Tislelizumab

Tislelizumab (BGB-A317) is BeiGene’s humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. We are evaluating zanubrutinib in combination with tislelizumab in an open-label, multi-center Phase 1b trial.

In combination with GAZYVA® (obinutuzumab)*

We are also evaluating zanubrutinib in combination with GAZYVA®, an approved anti-CD20 antibody therapy, in patients with B-cell lymphoma in a Phase 1b trial in Australia, the United States, and South Korea. Additionally, we are conducting a global pivotal Phase 2 trial of the zanubrutinib/GAZYVA® combination in relapsed or refractory follicular lymphoma.

*GAZYVA® is a registered trademark of Genentech, Inc.